2018 Section 5 - Rhinology and Allergic Disorders

DURHAM AND PENAGOS

J ALLERGY CLIN IMMUNOL FEBRUARY 2016

3 or 4 reactions were seen in the SLIT group. Thus both were effec- tive, and serious systemic reactions only occurred after SCIT. 47 Quirino et al 48 studied a 5-grass-pollen extract during 2 seasons in participants with seasonal rhinoconjunctivitis before and after 1 year of treatment. Twenty participants were allocated to receive active SLIT and placebo SCIT or active SCIT and placebo SLIT. No double placebo was included (see Table E5 ). After 12 months, the mean percentage reduction in total combined symptom and medication scores compared with the baseline year was 50% for SCIT and 51% for SLIT. Minor local reactions were confined to SCIT, and no systemic adverse events occurred in either group. 48 SCIT and SLIT appeared equivalent in efficacy and were well tolerated. Ventura et al 49 studied an extract of Juniperus ashei in 40 adults with cypress pollen–associated SAR. Ten received active SLIT drops, 10 received active SCIT, 10 received placebo SLIT drops, and 10 received placebo injections. An additional control group comprised 10 nonatopic subjects receiving no treatment (see Table E5 ). After 12 months, both groups receiving active treatment, but not placebo-treated subjects, showed a reduction in symptoms. Decreases in eosinophil cationic protein levels and eosinophil chemotactic activity in nasal lavage fluid correlated with the decreases in symptoms. No numeric comparison is possible from the data, and there was no record of adverse events. 49 Yukselen et al 38 carried out a 12-month randomized, double-blind, double-dummy trial of SLIT, SCIT, and placebo in 31 children with mite allergy and AR, mild asthma, and positive skin test responses and specific IgE levels to D pteronyssinus and D farinae . Compared with baseline, similar reductions in rhinitis symptom and medication scores were observed in participants treated with SLIT and SCIT but not in placebo-treated subjects. Regarding asthma symptom and medication scores, these were significantly reduced only in the SCIT-treated group. No systemic adverse reactions were reported in any of the groups. 38 In summary, in the only 4 double-blind head-to-head comparisons, there were no differences for SCIT versus SLIT in rhinitis symptom or medication scores. Limitations of these trials include small numbers, variable study design, inability to compare doses, and, in 3 of 4, elements that indicate a risk of bias. Whereas both SCIT and SLIT were effective for AR, as concluded by other recent reviews, 42,66,67 no firm conclusions can be drawn from the direct comparisons concerning the relative efficacy of the 2 treatment routes, whereas systemic adverse events were more common after SCIT. Five recent well-powered double-blind RCTs provide further evidence of the efficacy and safety of SLIT in patients with AR ( Table II ). 68-72 These 5 trials included 4022 subjects, which is almost equivalent to the 4589 participants included in the 49 trials evaluated in the Cochrane meta-analysis of SLIT. 36 Three trials of sublingual tablets were performed in patients with perennial rhinitis sensitized to house dust mite. 68-70 Tablets comprised a mixture of D pteronyssinus and D farinae and were administered daily for 12 months. Participants were adults and comprised a high proportion of subjects who were polysensitized (48% to 83%) and had comorbid mild asthma (29% to 100%). All 3 trials showed ev- idence of efficacy in rhinitis with a clear dose response and an 18% to 28% reduction in combined symptom-medication scores in the RECENT WELL-POWERED STUDIES OF SLIT (2014-2015)

FIG 3. SCIT versus SLIT: a balance of efficacy and safety.

active compared with placebo-treated groups. The largest immu- notherapy trial performed to date involved 1501 adults and children (age range, 5-65 years) with grass pollen ARC, of whom 85% were polysensitized and 25% had asthma. 72 Use of grass pollen tablets (containing 15 m g of Phl p 5) daily for 20 weeks resulted in a 20% decrease in rhinoconjunctivitis symptoms and a 23% decrease in total combined scores compared with placebo. Similarly, in patients with Japanese cedar allergy, SLIT drops (containing 3-5 m g of Cry j 1) daily for 18 months resulted in a 26%decrease in total combined nasal symptommedi- cation scores. 71 In these trials adverse events were reported in both the actively treated (59% to 86%) and placebo-treated (24% to 80%) groups. Local side effects (itching, swelling, and throat irritation) occurred in the active (41% to 89%) and placebo (12% to 21%) groups and were mild to moderate in intensity and generally well tolerated. Treatment-related adverse events resulted in withdrawal in both the active (0.6% to 6%) and placebo-treated (0.6% to 1%) groups. Although 51 serious adverse events were reported in 4 studies (0% to 4% of subjects receiving active SLIT and 0% to 3% receiving placebo), 68-71 only 6 were assessed as related to treatment. Adren- alinewas administered in 5 participants (4 in the active SLIT groups and 1 in the placebo group); in 2 subjects symptoms were assessed as unrelated to the study interventions (1 in the active SLIT group and 1 in the placebo group), 72 whereas 3 participants receiving active treatment received adrenaline because of local reactions in the absence of clear respiratory compromise or hypotension. Two of these participants discontinued treatment, 72 and 1 completed the trial. 70 In the study by Maloney et al, 72 1 participant receiving placebo treatment presented a moderate systemic reaction assessed as moderate anaphylaxis (wheezing, cough, and nasal congestion) on day 1. The patient was treated with b 2 -agonists and antihistamines; symptoms resolved, and the participant discontinued. 72 In a recent phase I RCT conducted in 12- to 17-year-old children who received sublingual house dust mite tab- lets or placebo, treatment was generally well tolerated, there were no systemic reactions, and side effects were mild to moderate in in- tensity (55% received active SLIT and 43% received placebo). Throat irritation was the most common local side effect (19% received active SLIT and 6% received placebo). 73 No fatalities were reported in any of these studies. SUMMARY AND CONCLUSIONS Both SCIT and SLIT are effective in reducing symptoms and requirement for rescue medication in patients with AR. The evidence base is stronger for patients with seasonal than perennial

163